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VEGF-induced effects on proliferation, migration and tight junctions are restored by ranibizumab (Lucentis) in microvascular retinal endothelial cells

¹ Department of Ophthalmology, University of Ulm Medical School, Ulm, Germany
² Department of Obstetrics and Gynecology, University of Ulm Medical School, Ulm, Germany

Correspondence to:
Dr H Deissler, Head of Research Laboratory, Department of Ophthalmology, University of Ulm Medical School, Prittwitzstrasse 43, D-89075 Ulm, Germany; heidrun.deissler{at}uniklinik-ulm.de

Background: Because vascular endothelial growth factor (VEGF) signalling is deregulated in diabetic retinopathy, the potential therapeutic effects of VEGF inhibitors such as the human VEGF-specific antibody ranibizumab are currently being tested. A study was undertaken to determine whether VEGF-stimulated processes in retinal endothelial cells are reversed by ranibizumab.

Methods: The influence of VEGF₁₂₁ and VEGF₁₆₅ on the proliferation and migration of immortalised bovine retinal endothelial cells (iBREC) was studied in the presence and absence of ranibizumab. In addition, the protein composition of tight junctions in the presence of VEGF and its inhibitor in iBREC was investigated.

Results: While both isoforms stimulated proliferation of iBREC, only VEGF₁₆₅ influenced cell migration. The addition of ranibizumab counteracted this stimulation without inhibition of the basal levels of migration and proliferation. Plasma membrane staining of the tight junction proteins occludin and claudin-1 disappeared in the presence of VEGF₁₆₅; there was no effect on claudin-5 and ZO-1 was only weakly affected. The addition of ranibizumab restored plasma membrane localisation of occludin and claudin-1. For claudin-1, the variation in total protein expression corresponded with the observed effects of VEGF₁₆₅ and ranibizumab.

Conclusion: Ranibizumab reverses proliferation and cell migration stimulated by VEGF and delocalisation of tight junction proteins induced by VEGF₁₆₅ in iBREC.

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Harminder S Dua and Arun D Singh
Br. J. Ophthalmol. 2008 92: 727. [Extract] [Full Text] [PDF]